Calcium channel function and regulation in beta 1- and beta 2-adrenoceptor
transgenic mice
Naunyn Schmiedebergs Arch Pharmacol, 369 (5):
490-5 (мая 2004)Foerster, Katharina Kaeferstein, Tomas Groner, Ferdi Engelhardt,
Stefan Matthes, Jan Koch, Walter J Lohse, Martin J Herzig, Stefan
Research Support, Non-U.S. Gov't Germany Naunyn-Schmiedeberg's archives
of pharmacology Naunyn Schmiedebergs Arch Pharmacol. 2004 May;369(5):490-5.
Epub 2004 Apr 9..Аннотация
Cardiac effects of catecholamines on the L-type calcium channel depend
on beta-adrenoceptor subtype (beta(1)- vs. beta(2)-adrenoceptor).
Chronic overexpression of these receptors leads to hypertrophy and
early death at moderate (beta(1)) or excessive (beta(2)) levels of
overexpression respectively. In order to examine the role of L-type
calcium channels in altered cardiomyocyte calcium homeostasis found
with beta(1)-adrenoceptor overexpression, and to understand the quantitative
differences between beta-adrenoceptor subtypes regarding calcium
channel regulation, we examined single channels in myocytes obtained
from beta(1)- and beta(2)-adrenoceptor transgenic mice. The effects
of the agonist isoproterenol were investigated and compared with
acute receptor stimulation in the respective non-transgenic littermates.
Channels from beta(1)-adrenoceptor transgenic mice have normal baseline
activity, and channel number is not reduced. This contrasts to previous
findings with beta(2)-adrenoceptor transgenic mice, where channel
activity is depressed. Isoproterenol is unable to stimulate channel
activity in both transgenic models. In conclusion, the L-type calcium
channel is not likely to be involved in alterations of calcium handling
of beta(1)-adrenoceptor transgenic myocytes. Furthermore, chronic
beta(1)-adrenoceptor overexpression does not depress channel activity,
giving another example of the difference between beta(1)- and beta(2)-adrenoceptor
signal transduction.